In 1582 Mikołaj Krzysztof "Sierotka" Radziwiłł, the Marshal of Lithuania, Voivode of Trakai–Vilnius and castellan of Šiauliai, started the construction of an imposing square three-storey "château". Although the works were based on a pre-existing structure of a medieval castle, the former fortifications were entirely turned into a renaissance-baroque house. Construction was completed by 1604, and they added several galleries half a century later. The château's corners were fortified with four octagonal towers.

In 1706, during the Great Northern War, Charles XII's army sacked the castle and destroyed its fortifications. Several decades later, the Radziwiłłs invited some German and Italian architects to substantially renovate and enlarge the castle. Antoni Zaleski decorated its yellow facades with baroque stucco work. The 16th-century castle gates were also reconstructed, and the two-storey gatehouse tower was crowned with a helm. It was at this time that the three separate buildings surrounding the central courtyard were joined into a single structure.

The most important structure in Nieśwież is the Corpus Christi Church (1587 to 1603), connected with the castle by a dam over a ditch and containing coffins of 72 members of the Radziwiłł family, each interred in a simple coffin made of birch and marked with Trąby coat of arms. Designed by the Italian architect Gian Maria Bernardoni (1541 to 1605), the church is considered the first Jesuit temple patterned after Il Gesù in Rome, the first domed basilica with Baroque facade in the world[citation needed] and the first baroque piece of architecture in Eastern Europe.

Apart from elaborate princely sepulchres, its interior features some late baroque frescoes from 1760s and the Holy Cross altar, executed by Venetian sculptors in 1583.

The main entrance to the princely residence

In 1772, following the third and last partition of Polish–Lithuanian Commonwealth, the castle was seized by Russian forces and the Radziwiłł family was expelled. Soon afterwards the Lithuanian Archive was transferred to Saint Petersburg (where it still remains today), while the majority of works of art gathered in the palace were distributed among various Russian and Polish nobles in support of Catherine the Great. Abandoned both by the original owners and by the Russian army, the palace gradually fell into disrepair. However, it was restored by the Radziwiłłs and between 1881 and 1886 the castle's interiors were renovated by Prince Antoni Radziwiłł and his French wife, Marie de Castellane. They also designed a landscape park in English style. With an area of more than one square kilometre, the park is one of the biggest such facilities in Europe.

The ongoing reconstruction has drawn sharp criticism for its "unjustified reconstruction" of several long-demolished structures, notably a bell-tower. In 2002, the upper storey of the residence was destroyed by fire. Six years later, the Belarus edition of the Komsomolskaya Pravda reported that a substantial section of the castle, dating from the 18th century, had been entirely demolished on account of "rotten brick" (see photo).